10
Internal validity Did the control group receive optimal treatment? Was the sample size adequate to identify any relevant difference? Was the dose of the control group adequate?

11
Internal validity Did the control group receive optimal treatment? Did the published results refer to the primary variable? Was the sample size adequate to identify any relevant difference? Was the dose of the control group adequate?

14
Internal validity Did the control group receive optimal treatment? Have all the trial results been published? Did the published results refer to the primary variable? Was the sample size adequate to identify any relevant difference? Was the dose of the control group adequate?

17
Internal validity Did the control group receive optimal treatment? Were the results presented as a relative risk reduction, or as an absolute risk reduction? Have all the trial results been published? Did the published results refer to the primary variable? Was the sample size adequate to identify any relevant difference? Was the dose of the control group adequate?

42
Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (ATP III) Financial Disclosure: Dr Grundy has received honoraria from Merck, Pfizer, Sankyo, Bayer, and Bristol-Myers Squibb. Dr Hunninghake has current grants from Merck, Pfizer, Kos Pharmaceuticals, Schering Plough, Wyeth Ayerst, Sankyo, Bayer, AstraZeneca, Bristol-Myers Squibb, and G. D. Searle; he has also received consulting honoraria from Merck, Pfizer, Kos Pharmaceuticals, Sankyo, AstraZeneca, and Bayer. Dr McBride has received grants and/or research support from Pfizer, Merck, Parke-Davis, and AstraZeneca; has served as a consultant for Kos Pharmaceuticals, Abbott, and Merck; and has received honoraria from Abbott, Bristol-Myers Squibb, Novartis, Merck, Kos Pharmaceuticals, Parke-Davis, Pfizer, and DuPont. Dr Pasternak has served as a consultant for and received honoraria from Merck, Pfizer, and Kos Pharmaceuticals, and has received grants from Merck and Pfizer. Dr Stone has served as a consultant and/or received honoraria for lectures from Abbott, Bayer, Bristol-Myers Squibb, Kos Pharmaceuticals, Merck, Novartis, Parke-Davis/Pfizer, and Sankyo. Dr Schwartz has served as a consultant for and/or conducted research funded by Bristol-Myers Squibb, AstraZeneca, Merck, Johnson & Johnson-Merck, and Pfizer.

46
Conclusions The RCT is the best epidemiological method for causal inference However, it is often performed in a way which favours the sponsors treatment: –In its design –In data analysis and interpretation –In the publication of results At best, RCTs are one of many pieces of evidence about therapeutic interventions

47
Conclusions The appraisal of innovation should not only take into account the so-called EBM, but also other evidence: –Pharmacodynamics –Pharmacokinetics –Availability of therapeutic alternatives The medical literature is no longer reliable for valid information Research should be performed, analyzed and published in a way which should be independent from commercially interested parties